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Effect of lamin-A expression on migration and nuclear stability of ovarian cancer cells.

Abstract：

OBJECTIVE:Nuclear lamina plays important roles in nuclear shape and mechanical stability. Many studies demonstrated that defects of lamin-A were associated with several diseases, but little research was found on its potential roles in ovarian cancer. METHODS:GEPIA and GEO database were used to analyze lamin-A in ovarian tissues, followed by assessing lamin-A and prognosis of ovarian cancer patients with Kaplan-Meier plotter. Then, transient transfected HO-8910 cells with shRNA to knockdown lamin-A. Knockdown efficiency was determined by western blot, qRT-PCR and immunofluorescence. Meanwhile, lamin-A was overexpressed in HO-8910 PM cells. Then, 2D migration, 3D migration through 3 μm and 8 μm pores were carried out, followed by immunofluorescence and TEM observation. RESULTS:Lamin-A tended to be lower in ovarian cancer, and higher expression of lamin-A was associated with better survival. After lamin-A knockdown, 2D and 3D migration (3 μm, 8 μm) abilities of HO-8910 cells were significantly increased (p < 0.001), while overexpression of lamin-A in HO-8910PM impeded migration. Meanwhile, when HO-8910 cells migrated through 3 μm pores, nuclei became strikingly elongated, and down-regulation of lamin-A promoted nuclear plasticity, making the circularity of nucleus increased. Besides, further knockdown group had the highest proportion of γ-H2AX, with micronuclei forming. Furthermore, western blot showed that the expression of BRCA1, Ku80 and Rad50 decreased significantly after further knockdown, suggesting impairment of DNA damage repair. CONCLUSIONS:Lamin-A was down-regulated in ovarian cancer, and higher lamin-A was associated with better prognosis. Nuclei with high lamin-A were severely deformed through constricted pores. Moderate lamin-A enhanced nuclear plasticity, so as to strengthen migration ability. When lamin-A was further knockdown, ovarian cancer cells that migrated through restricted pores decreased, with DNA damage, genomic instability and impairment of DNA damage repair.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Wang Y,Jiang J,He L,Gong G,Wu X

doi

10.1016/j.ygyno.2018.10.030

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

166-176

issue

1

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(18)31313-1

journal_volume

152

pub_type

杂志文章

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